Protein kinase C beta type - Bos taurus (Bovine)

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Preferred order of sections

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequence databases

3D structure databases

Protein-protein interaction databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Family and domain databases

Other

Contribute

Send feedback

Read comments (?) or add your own

P05126 (KPCB_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 139. History...

Clusters with 100%, 90%, 50% identity |

Documents (1) |

Third-party data

text xml rdf/xml gff fasta

Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Protein names

Recommended name:
Protein kinase C beta type
Short name=PKC-B
Short name=PKC-beta
EC=2.7.11.13

Gene names

Name:	PRKCB
Synonyms:	PRKCB1

Organism

Bos taurus (Bovine) [Reference proteome]

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Sequence length	671 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

Function	Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity. Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A. In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. May participate in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Binds 3 calcium ions per subunit. The ions are bound to the C2 domain By similarity.
Enzyme regulation	Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-500 (activation loop of the kinase domain), Thr-642 (turn motif) and Ser-661 (hydrophobic region), need to be phosphorylated for its full activation. Specifically inhibited by enzastaurin (LY317615) By similarity.
Subunit structure	Interacts with PDK1. Interacts in vitro with PRKCBP1. Interacts with PHLPP1 and PHLPP2; both proteins mediate its dephosphorylation. Interacts with KDM1A/LSD1, PKN1 and ANDR By similarity.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Membrane; Peripheral membrane protein By similarity.
Post-translational modification	Phosphorylation on Thr-500 within the activation loop renders it competent to autophosphorylate. Subsequent autophosphorylation of Thr-642 maintains catalytic competence, and autophosphorylation on Ser-661 appears to release the kinase into the cytosol. Autophosphorylation on other sites i.e. in the N-terminal and hinge regions have no effect on enzyme activity. Phosphorylation at Tyr-662 by SYK induces binding with GRB2 and contributes to the activation of MAPK/ERK signaling cascade By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily. Contains 1 AGC-kinase C-terminal domain. Contains 1 C2 domain. Contains 2 phorbol-ester/DAG-type zinc fingers. Contains 1 protein kinase domain.

Keywords
Biological process	Adaptive immunity Apoptosis Immunity Transcription Transcription regulation
Cellular component	Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat Zinc-finger
Ligand	ATP-binding Calcium Metal-binding Nucleotide-binding Zinc
Molecular function	Chromatin regulator Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell activation Inferred from sequence or structural similarity. Source: UniProtKB B cell receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW calcium ion transport Inferred from electronic annotation. Source: Compara cellular calcium ion homeostasis Inferred from electronic annotation. Source: Compara cellular response to carbohydrate stimulus Inferred from electronic annotation. Source: Compara intracellular signal transduction Inferred from electronic annotation. Source: InterPro negative regulation of glucose transport Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of insulin receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of B cell receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of NF-kappaB transcription factor activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of angiogenesis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of vascular endothelial growth factor receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW androgen receptor binding Inferred from sequence or structural similarity. Source: UniProtKB calcium channel regulator activity Inferred from electronic annotation. Source: Compara chromatin binding Inferred from sequence or structural similarity. Source: UniProtKB histone binding Inferred from sequence or structural similarity. Source: UniProtKB histone kinase activity (H3-T6 specific) Inferred from sequence or structural similarity. Source: UniProtKB ligand-dependent nuclear receptor transcription coactivator activity Inferred from sequence or structural similarity. Source: UniProtKB protein kinase C activity Inferred from electronic annotation. Source: EC zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Initiator methionine

Removed By similarity

Chain

2 – 671

670

Protein kinase C beta type

PRO_0000055683

Domain

173 – 260

Domain

342 – 600

259

Protein kinase

Domain

601 – 669

AGC-kinase C-terminal

Zinc finger

36 – 86

Phorbol-ester/DAG-type 1

Zinc finger

101 – 151

Phorbol-ester/DAG-type 2

Nucleotide binding

348 – 356

ATP By similarity

Active site

466

Proton acceptor By similarity

Metal binding

186

Calcium 1; via carbonyl oxygen By similarity

Metal binding

187

Calcium 1 By similarity

Metal binding

187

Calcium 2 By similarity

Metal binding

193

Calcium 2 By similarity

Metal binding

246

Calcium 1 By similarity

Metal binding

246

Calcium 2 By similarity

Metal binding

247

Calcium 2; via carbonyl oxygen By similarity

Metal binding

248

Calcium 1 By similarity

Metal binding

248

Calcium 2 By similarity

Metal binding

248

Calcium 3 By similarity

Metal binding

251

Calcium 3 By similarity

Metal binding

252

Calcium 3; via carbonyl oxygen By similarity

Metal binding

254

Calcium 1 By similarity

Metal binding

254

Calcium 3 By similarity

Binding site

371

ATP By similarity

Modified residue

N-acetylalanine By similarity

Modified residue

Phosphoserine; by autocatalysis Potential

Modified residue

Phosphothreonine; by autocatalysis Potential

Modified residue

195

Phosphotyrosine By similarity

Modified residue

250

Phosphothreonine; by autocatalysis By similarity

Modified residue

324

Phosphothreonine; by autocatalysis Potential

Modified residue

500

Phosphothreonine; by PDPK1 By similarity

Modified residue

504

Phosphothreonine By similarity

Modified residue

635

Phosphothreonine; by autocatalysis By similarity

Modified residue

642

Phosphothreonine; by autocatalysis By similarity

Modified residue

661

Phosphoserine; by autocatalysis By similarity

Modified residue

662

Phosphotyrosine; by SYK By similarity

Alternative sequence

622 – 671

RDKRD…FVINV → CGRNAENFDRFFTRHPPVLT PPDQEVIRNIDQSEFEGFSF VNSEFLKPEVKS in isoform Beta-II.

VSP_039222

Sequence conflict

576

M → I in AAA30703. Ref.2

Sequence		Length	Mass (Da)
Isoform Beta-I (PRKCB1) [UniParc]. Last modified May 18, 2010. Version 4. Checksum: 1F31D6A9D3C4C61F Show »	FASTA	671	76,790
10 20 30 40 50 60 MADPAAGPPP SEGEESTVRF ARKGALRQKN VHEVKNHKFT ARFFKQPTFC SHCTDFIWGF 70 80 90 100 110 120 GKQGFQCQVC CFVVHKRCHE FVTFSCPGAD KGPASDDPRS KHKFKIHTYS SPTFCDHCGS 130 140 150 160 170 180 LLYGLIHQGM KCDTCMMNVH KRCVMNVPSL CGTDHTERRG RIYIQAHIER EVLIVVVRDA 190 200 210 220 230 240 KNLVPMDPNG LSDPYVKLKL IPDPKSESKQ KTKTIKCSLN PEWNETFRFQ LKESDKDRRL 250 260 270 280 290 300 SVEIWDWDLT SRNDFMGSLS FGISELQKAG VDGWFKLLSQ EEGEYFNVPV PPEGSEGNEE 310 320 330 340 350 360 LRQKFERAKI GPGPKTPEEK TTNTISKFDN NGNRDRMKLT DFNFLMVLGK GSFGKVMLSE 370 380 390 400 410 420 RKGTDELYAV KILKKDVVIQ DDDVECTMVE KRVLALPGKP PFLTQLHSCF QTMDRLYFVM 430 440 450 460 470 480 EYVNGGDLMY HIQQVGRFKE PHAVFYAAEI AIGLFFLQSK GIIYRDLKLD NVMLDSEGHI 490 500 510 520 530 540 KIADFGMCKE NIWDGVTTKT FCGTPDYIAP EIIAYQPYGK SVDWWAFGVL LYEMLAGQAP 550 560 570 580 590 600 FEGEDEDELF QSIMEHNVAY PKSMSKEAVA ICKGLMTKHP GKRLGCGPEG ERDIKEHAFF 610 620 630 640 650 660 RYIDWEKLER KEIQPPYKPK ARDKRDTSNF DKEFTRQPVE LTPTDKLFIM NLDQNEFAGF 670 SYTNPEFVIN V « Hide
Isoform Beta-II (PRKCB2) [UniParc]. Checksum: 61711D08707B005B Show »	FASTA	673	76,933
10 20 30 40 50 60 MADPAAGPPP SEGEESTVRF ARKGALRQKN VHEVKNHKFT ARFFKQPTFC SHCTDFIWGF 70 80 90 100 110 120 GKQGFQCQVC CFVVHKRCHE FVTFSCPGAD KGPASDDPRS KHKFKIHTYS SPTFCDHCGS 130 140 150 160 170 180 LLYGLIHQGM KCDTCMMNVH KRCVMNVPSL CGTDHTERRG RIYIQAHIER EVLIVVVRDA 190 200 210 220 230 240 KNLVPMDPNG LSDPYVKLKL IPDPKSESKQ KTKTIKCSLN PEWNETFRFQ LKESDKDRRL 250 260 270 280 290 300 SVEIWDWDLT SRNDFMGSLS FGISELQKAG VDGWFKLLSQ EEGEYFNVPV PPEGSEGNEE 310 320 330 340 350 360 LRQKFERAKI GPGPKTPEEK TTNTISKFDN NGNRDRMKLT DFNFLMVLGK GSFGKVMLSE 370 380 390 400 410 420 RKGTDELYAV KILKKDVVIQ DDDVECTMVE KRVLALPGKP PFLTQLHSCF QTMDRLYFVM 430 440 450 460 470 480 EYVNGGDLMY HIQQVGRFKE PHAVFYAAEI AIGLFFLQSK GIIYRDLKLD NVMLDSEGHI 490 500 510 520 530 540 KIADFGMCKE NIWDGVTTKT FCGTPDYIAP EIIAYQPYGK SVDWWAFGVL LYEMLAGQAP 550 560 570 580 590 600 FEGEDEDELF QSIMEHNVAY PKSMSKEAVA ICKGLMTKHP GKRLGCGPEG ERDIKEHAFF 610 620 630 640 650 660 RYIDWEKLER KEIQPPYKPK ACGRNAENFD RFFTRHPPVL TPPDQEVIRN IDQSEFEGFS 670 FVNSEFLKPE VKS « Hide

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Multiple, distinct forms of bovine and human protein kinase C suggest diversity in cellular signaling pathways." Coussens L., Parker P.J., Rhee L., Yang-Feng T.L., Chen E., Waterfield M.D., Francke U., Ullrich A. Science 233:859-866(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-II).
[2]	NIH - Mammalian Gene Collection (MGC) project Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA-I). Strain: Hereford. Tissue: Fetal pons.
[3]	"The molecular heterogeneity of protein kinase C and its implications for cellular regulation." Nishizuka Y. Nature 334:661-665(1988) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.

Sequence databases
EMBL GenBank DDBJ	M13974 mRNA. Translation: AAA30703.1. BC140620 mRNA. Translation: AAI40621.1.
IPI	IPI00691407. IPI00837740.
PIR	KIBOC2. A24664.
RefSeq	NP_777012.1. NM_174587.1.
UniGene	Bt.5435.
3D structure databases
ProteinModelPortal	P05126.
SMR	P05126. Positions 37-288, 339-668.
ModBase	Search...
Protein-protein interaction databases
STRING	9913.ENSBTAP00000027870.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSBTAT00000027870; ENSBTAP00000027870; ENSBTAG00000020921. ENSBTAT00000042942; ENSBTAP00000040548; ENSBTAG00000020921.
GeneID	282325.
KEGG	bta:282325.
Organism-specific databases
CTD	5579.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00640000091170.
HOGENOM	HOG000233022.
HOVERGEN	HBG108317.
InParanoid	P05126.
KO	K02677.
OMA	QAHIDRE.
OrthoDB	EOG40ZQX0.
Enzyme and pathway databases
BRENDA	2.7.11.13. 908.
Reactome	REACT_114534. Signal Transduction.
Family and domain databases
InterPro	IPR000961. AGC-kinase_C. IPR000008. C2_Ca-dep. IPR008973. C2_Ca/lipid-bd_dom_CaLB. IPR020477. C2_dom. IPR018029. C2_membr_targeting. IPR020454. DAG/PE-bd. IPR011009. Kinase-like_dom. IPR017892. Pkinase_C. IPR002219. Prot_Kinase_C-like_PE/DAG-bd. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR014375. Protein_kinase_C_a/b/g. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00130. C1_1. 2 hits. PF00168. C2. 1 hit. PF00069. Pkinase. 1 hit. PF00433. Pkinase_C. 1 hit. [Graphical view]
PIRSF	PIRSF000550. PKC_alpha. 1 hit.
PRINTS	PR00360. C2DOMAIN. PR00008. DAGPEDOMAIN.
SMART	SM00109. C1. 2 hits. SM00239. C2. 1 hit. SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF49562. C2_CaLB. 1 hit. SSF56112. Kinase_like. 1 hit.
PROSITE	PS51285. AGC_KINASE_CTER. 1 hit. PS50004. C2. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS00479. ZF_DAG_PE_1. 2 hits. PS50081. ZF_DAG_PE_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	20806122.

Entry name

KPCB_BOVIN

Accession

Primary (citable) accession number: P05126
Secondary accession number(s): A5D7N0

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	May 18, 2010
Last modified:	April 3, 2013
This is version 139 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Beta-I (identifier: P05126-1)

Also known as: PRKCB1;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Beta-II (identifier: P05126-2)

Also known as: PRKCB2;

The sequence of this isoform differs from the canonical sequence as follows:
622-671: RDKRDTSNFD...YTNPEFVINV → CGRNAENFDR...SEFLKPEVKS